Activation of Nrf2 signaling prevents insulitis in NOD mice. (A)
Representative images of pancreatic islets from hyperglycemic (blood glucose
>400 mg/dL) and normoglycemic (blood glucose <150 mg/dL)
NOD::Keap1FA/+ mice (left and
middle panels, respectively) and normoglycemic
NOD::Keap1FA/– mice
(right panel) at 24 weeks of age. Bar, 100 μm. Arrowhead, extensive
inflammatory cell infiltration in the islets. (B) Percentage of islets with
insulitis in the NOD mice. Nine to 15 islets of each mouse were examined for
percentage of insulitis in the
NOD::Keap1FA/+
(n=10) and
NOD::Keap1FA/–
(n=5) mice, respectively. The mean value of individual mice
is shown. The bar represents the median. (C) Distribution of the insulitis
scores for the NOD mice. The percentages of islets with each insulitis grade
were calculated using pooled values from 70 to 130 islets from the
NOD::Keap1FA/+
(n=10) and
NOD::Keap1FA/–
(n=5) mice. (D) Total insulitis scores for individual NOD
mice. Nine to 15 islets in each mouse were examined, and the 5-graded scoring
scale (0, 1, 2, 3 and 4) multiplied by the islet number for each grade was
summed up for each individual mouse. The mean value is shown in
NOD::Keap1FA/+
(n=10) and
NOD::Keap1FA/–
(n=5) mice. The bar represents the median. Scoring scale:
grade 0, no infiltration; grade 1, predominantly peri-islet mononuclear cell
infiltration; grade 2, infiltration in 25–50% of the islets; grade 3,
infiltration in 50–75% of the islets; and grade 4, infiltration in
>75% of the islets. Mann-Whitney U test (B) and Student’s
t-test (D) were applied. No statistical analysis was
performed in (C). *P<0.05.